Introduction Mitochondrial diseases are multisystem disorders in which defects in oxidative phosphorylation disrupt cellular bioenergetics and redox signaling across the vasculature and heart. Because mitochondrial function is closely linked to endothelial nitric oxide (NO) production, we hypothesized that mitochondrial diseases manifest as a NO-deficiency endotheliopathy affecting conduit and microvascular function. To evaluate this, we performed a systematic review with quantitative synthesis of human studies reporting vascular reactivity, biochemical NO production, or myocardial metabolic imaging, aiming to define the magnitude of impairment and responsiveness to NO-precursor therapy ( l -arginine or l -citrulline). Methods Following PRISMA 2020 guidelines, we conducted a comprehensive search (inception–October 2025) identifying clinical studies of genetically or clinically confirmed mitochondrial disease with quantitative endothelial or bioenergetic endpoints. Eligible measures included flow-mediated dilation (FMD), reactive hyperemia index (RHI), passive-leg-movement (PLM) hyperemia, absolute synthesis rate of NO metabolites (ASR NOm), and positron emission tomography (PET)-derived myocardial oxidative indices ( k mono , DP/ k mono ). Quantitative synthesis used Hedges g for between-group comparisons and standardized mean change (SMC) for within-subject responses. Risk of bias was evaluated using ROBINS-I and a modified Newcastle–Ottawa Scale. Results Seven studies met these inclusion criteria, comprising 76 mitochondrial-disease subjects and 81 controls (ages 8–63 years). Across all vascular and metabolic domains, mitochondrial disease was associated with marked endothelial and bioenergetic impairment. Macro- and microvascular dysfunction, reflected by reduced FMD, RHI, and PLM hyperemia, demonstrated severe endothelium-specific abnormalities. Biochemical assays showed diminished NO synthesis. Myocardial PET imaging revealed reduced oxidative rate constants and increased energetic inefficiency despite preserved perfusion. Nitric oxide synthesis-precursor therapy was associated with improved endothelial reactivity (increased FMD, RHI, and ASR NOm) and significant, modest improvements in myocardial oxidative metabolism, consistent with partial restoration of endothelial NO signaling. Effect sizes collectively supported a reversible NO-deficiency endotheliopathy. The risk-of-bias assessment indicated moderate-to-good methodological quality, with limitations primarily related to small sample sizes and nonrandomized designs. Conclusions Mitochondrial disease is characterized by significant impairments in vascular reactivity, NO signaling, and myocardial bioenergetics. Improvements in endothelial function and NO synthesis following l -arginine or l -citrulline supplementation are consistent with a role for impaired endothelial NO signaling in the vascular manifestations of mitochondrial disease. These findings highlight the vascular endothelium as a potential therapeutic target and underscore the need for future clinical intervention trials that use standardized vascular and bioenergetic endpoints.
The inaugural United Mitochondrial Disease Foundation (UMDF) Mitochondrial Medicine 2025 Masterclass focused on primary mitochondrial diseases (PMDs) especially primary mitochondrial myopathies (PMMs) and thymidine kinase 2 deficiency (TK2d). The Masterclass featured leading US experts in the field, providing the latest scientific and clinical knowledge, as well as patients and caregivers sharing their lived experience of mitochondrial diseases. In this report, we summarize the key highlights of each presentation. An overview of PMM featuring the etiologies of different PMMs and key features of notable PMMs, was followed by a presentation discussing the practical clinical processes of diagnosing PMM, how the roles of clinicians have evolved as diagnostic technology has improved, and actions clinicians can take to maximize the chances of an early, accurate diagnosis. Real-world case studies highlighted variations in disease presentation among the wide range of PMMs, which was followed by an in-depth review of clinical assessments and symptom management for PMM across organ systems. Multisystemic disorders like PMM require multidisciplinary management, in both a chronic and acute setting, and two experts discussed the practical workflow for clinicians to build a multidisciplinary model of care at their hospitals, the roles and responsibilities of the lead coordinator and each subspecialist, and practical steps that clinicians can take to manage acute care coordination and decrease acute care utilization. A hypothetical case study of TK2d (based on real patients) brought together the different aspects of PMM discussed during the Masterclass, while the patient perspective presentations allowed patients and caregivers to discuss the real-world impact that the diagnostic and care journey had on them and their families. This Educational Masterclass provided detailed knowledge of PMM designed to provide the next generation of clinicians and investigators with practical, actionable guidance and resources they could utilize to make a difference in the lives of patients with PMM.
Mucopolysaccharidosis type I (MPS-I) is an inherited lysosomal storage disorder characterized by alpha-L-iduronidase deficiency, leading to progressive multi-organ damage and fatal complications. Early treatment is crucial to improve outcomes, particularly in patients with severe phenotypes. We present the first case of successful allogeneic bone marrow transplantation (BMT) for MPS-I in Vietnam. A 10-month-old girl experienced coarse facial features, congenital dermal melanocytosis spots, kyphoscoliosis developmental delay. Laboratory analyses revealed reduced alpha-L-iduronidase activity and elevated urinary glycosaminoglycans, genetic mutations identified two heterozygous mutations in the IDUA gene, confirmed the diagnosis of MPS-I. At 3 years old, she underwent allogeneic BMT from an HLA-matched sibling donor following conditioning regimen with busulfan, cyclophosphamide, antithymocyte globulin. Neutrophil engraftment was achieved on day +24, and platelet engrafted on day +32. The post-transplant course was complicated by respiratory deterioration requiring 5 days of mechanical ventilation, which was promptly managed and resolved. No graft-versus-host disease occurred. Post-transplant chimerism showed 95.77% donor-derived cells on day +30 and remained stable at 100% from 2 months. The patient demonstrated improvement in clinical symptoms, accompanied by alpha-L-iduronidase activity returned to normal range, urinary glycosaminoglycan levels decreased and remained stable during follow-up. At 12 months, she demonstrated complete immune reconstitution. This case suggests that allogeneic BMT may be a therapeutic approach for patients with MPS-I in resource-limited settings.
Background: While somatic mitochondrial dysfunction occurs in diverse cancers, the association between oncogenesis and germline mitochondrial gene pathogenic variants remains unclear. Further, few clinical observations have been reported of cancer occurring in primary mitochondrial disease (PMD) patients. Objectives: To improve understanding of the potential modulating role for PMD gene disorders in cancer prevalence. Design: 727 individuals, including 100 with PMD, from 97 unrelated families were retrospectively surveyed to assess their history of individual cancer occurrence. Methods: We evaluated survey responses by characterizing the cancer prevalence among the study cohort and comparing to the general U.S. population via the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database. Odds ratio calculation was performed to determine the association of survey responses and cancer prevalence. Results: Although overall cancer prevalence in PMD probands and their families was elevated compared to the NCI SEER rate (8800 vs 5600 cases per 100,000), odds ratio calculation determined that PMD did not significantly increase the likelihood of developing cancer, with a non-significant trend observed toward less cancer occuring in PMD that needs to be explored in further studies. Cancer prevalence was significantly correlated with advanced age. Significantly reduced prevalence of prostate cancer was seen across the entire cohort. Surprisingly, while low absolute prevalence ( n = 3), a 9-fold increased odds ratio of cancer was seen in POLG patients relative to those with other causes of PMD. Conclusion: No evidence of increased cancer odds was identified in a cohort of PMD patients and their close relatives. Interestingly, a possible inverse association, which did not reach statistical significance, was suggested between mitochondrial disease status and cancer odds. Future prospective investigations in larger PMD kindreds are warranted to validate and evaluate potential mechanistic relations between cancer prevalence and PMD.
Background:Thymidine kinase 2 deficiency (TK2d) is an ultra-rare autosomal recessive mitochondrial disease characterized by progressive myopathy. Objectives:To understand patient experiences and the impact of TK2d on patient quality of life (QoL), and to explore support needs. Design:A cross-sectional international online survey. Methods:The survey for the Assessment of TK2d Patient Perspectives (ATP) study, co-created with patient advocates, included multiple-choice questions, verbal rating scales, and open free-text questions. Patients of all ages with a self-reported genetic diagnosis of TK2d were eligible to participate, either directly or through a caregiver proxy. The patient, caregiver proxy, or bereaved caregiver proxy answered questions on demographics, signs/symptoms, impacts on health-related QoL (HRQoL), support needs, healthcare resource use, and overall experience of living with TK2d. Quantitative data were summarized with descriptive statistics. Qualitative data were analyzed using inductive thematic analysis. Results:Responses for 32 patients (24 patient and 8 caregiver proxy responses) were collected between September 2023 and February 2024. All patients experienced myopathic symptoms. The most frequently reported impact of TK2d was on patients' ability to perform basic activities of daily living (26/32), including difficulties in walking (22/32), eating/swallowing (19/32), and breathing (25/32). The proportions of patients reporting a moderate or severe impact of breathing and walking difficulties on HRQoL, and the proportions requiring medical devices, were higher for those with an earlier age of TK2d symptom onset (⩽2, vs >2 to ⩽12, or >12 years). For most patients, TK2d also had a negative impact on mood, social and leisure activities, and employment/education. Progressive loss of abilities, increasing dependency on others, and medical equipment use contributed to mental and emotional burdens. Conclusion:These quantitative and qualitative analyses of patients' lived experiences highlight the substantial, progressive, and wide-ranging burden of TK2d.
β-thalassemia is an inherited blood disorder characterized by chronic anemia, ineffective erythropoiesis, and in its most severe form, lifelong transfusion dependence. The standard of care for transfusion-dependent thalassemia (TDT) is regular red blood cell transfusions to relieve the anemia and suppress ineffective erythropoiesis and iron chelation therapy to mitigate morbidity and mortality related to iron overload. Allogeneic hematopoietic stem cell transplantation is a curative option but is only available to patients with an appropriate donor and carries risks of graft-versus-host disease and other transplant-related morbidity. In recent years, the therapeutic landscape for TDT has changed dramatically with the approval of two autologous gene therapies in the United States: betibeglogene autotemcel (beti-cel) and exagamglogene autotemcel (exa-cel). Clinical trials for both gene therapies have demonstrated high rates of sustained transfusion independence for both pediatric and adult age groups. However, despite these advances, challenges remain. Gene therapy requires myeloablative busulfan-based conditioning chemotherapy, which carries the risk of short- and long-term toxicities. Furthermore, centralized manufacturing and high treatment costs are likely to limit access to gene therapy. In this review, we discuss the available clinical trial and real-world data for beti-cel and exa-cel. We describe how gene therapy fits into the current treatment landscape and introduce areas of ongoing investigation to improve access to transformative therapy for TDT.
Background: Outcome-based agreements (OBAs) may facilitate earlier patient access to promising therapies, particularly when evidence is limited. The authors of this paper investigated how to operationalize an OBA using real-world data (RWD) from the Canadian Neuromuscular Disease Registry (CNDR). Objective: The first objective of this research was to determine which spinal muscular atrophy (SMA) health outcomes in the CNDR are suitable for an OBA. The second objective was to evaluate the current process of data collection in the CNDR and explore how to operationalize data processes to support an OBA, including identifying gaps and proposing solutions. Design: This qualitative expert-led assessment was conducted through a series of focus group discussions with selected experts. Methods: A selected group of experts participated in 17 focus group meetings. The ability of the CNDR to generate real-world evidence (RWE) for an OBA was evaluated for eight SMA health outcomes. The criteria used were data readiness, interpretability, and timeframe within the CNDR. Next, the processes involved were evaluated, specifically to determine how data tracking within the CNDR could be operationalized for an OBA, including identifying gaps and possible solutions. Based on the findings, the group proposed a future state for an OBA process using the CNDR. The group followed up with stakeholder feedback interviews to validate the findings of this research and to gather insights. Results: Five SMA outcomes within the CNDR were identified as potentially suitable outcomes for OBA. Three process gaps were identified in the current state of the CNDR, and corresponding solutions were proposed. A proposed future-state process flow for CNDR was developed to support RWE generation for OBA. Conclusions: Expert consultations suggest that operationalizing an OBA using CNDR RWD is feasible.
Background: Fabry disease is rare and multisystemic, necessitating a disease-specific quality of life scale to assess changes in quality of life. We developed the Adult Fabry Disease Quality of Life scale to measure the quality of life of adult patients with Fabry disease. Objectives: To confirm the reliability of the Adult Fabry Disease Quality of Life scale using the test–retest method and calculate the minimal important change. Design: This study was based on two questionnaire surveys conducted at approximately 2-week intervals in November and December 2024 in Japan. Methods: Twenty-eight participants completed questionnaires consisting of background information, the Adult Fabry Disease Quality of Life scale, and the Short Form-8. In the second survey, an anchor question with a 7-point Likert scale was added to assess changes in general health. The intraclass correlation coefficient for reliability and Cronbach’s alpha coefficient for internal consistency were calculated. For minimal important changes, the average value of the smallest change group for the anchor question was calculated. Results: The intraclass correlation coefficients for each factor and the total score on the Adult Fabry Disease Quality of Life scale were 0.892–0.946. Cronbach’s alpha coefficient was 0.948 for the first survey and 0.956 for the second. In response to the anchor question, three participants (13.0%) felt a little worse, and three (13.0%) felt a little better. Those who felt a little worse and those who felt a little better showed improvements in quality of life of 3.7 and 5.3 points, respectively. Conclusion: The Adult Fabry Disease Quality of Life scale is highly reproducible at 2-week intervals. Defining the minimum important change was not possible, which is important when used as an outcome. Future studies should establish it using the anchor method. Trial Registration: This prospective study was registered with the UMIN-CTR on September 1, 2024 (No. UMIN000055144).
Background: Clinical studies have begun to evaluate therapeutic approaches to address the widespread neurodevelopmental and mental health challenges associated with a group of genetic syndromes known as "RASopathies." However, the perspectives of patients and families regarding the relevance and accessibility of such treatment approaches have not been studied.Objectives: To assess the mental healthcare needs and treatment experiences encountered by individuals with RASopathies and caregivers.Design: Directed content analysis of focus group and interview transcripts.Methods: We qualitatively analyzed data from four virtual focus groups comprised of caregivers (n = 21) of youth with RASopathies and a series of individual interviews with young adults (n = 11) with RASopathies. Perspectives on primary neurodevelopmental and mental health concerns, treatment history, and care accessibility were explored using a directed content analysis framework.Results: Consistent with prior research, participants reported that attention/executive functioning, mood, and social concerns were common; anxiety was a particularly frequent comorbidity. Mental health concerns varied across settings and frequently interfaced with physical health symptoms. Barriers to care included poor accessibility of services, adverse medication effects, and a lack of provider experience or knowledge. Addressing neurodevelopmental and mental health symptoms effectively often necessitates family resilience and advocacy on the part of patients and their caregivers. Emergent themes uncovered needs for provider training pertaining to rare diseases, trauma-informed care, and improved community awareness regarding RASopathies.Conclusion: This study identified a set of actionable items to inform research, care delivery, and advocacy that reflect the expressed needs and lived experiences of participants representing both caregivers and patients with RASopathies.
Background: Pyridoxine-dependent epilepsy (PDE) due to biallelic pathogenic variants in ALDH7A1 (PDE-ALDH7A1) is an metabolic disease of lysine catabolism. Current standard treatment includes pyridoxine, arginine, and lysine- or protein-restricted diet. Pyridoxine treats seizures. Arginine and lysine- or protein-restricted diet decrease elevated α-aminoadipic semialdehyde (α-AASA) and Δ1- piperideine-6-carboxylate (P6C) levels to improve neurodevelopmental outcomes. We previously reported abnormalities in tricarboxylic acid (TCA) cycle and electron transport chain in PDE-ALDH7A1. We report a new patient with PDE-ALDH7A1 who did not show any improvements in neurodevelopment on the current standard therapy. We hypothesized that triheptanoin will provide substrate to TCA cycle and improve abnormal energy metabolism leading to improvements in neurodevelopmental outcome. Objective: To treat this patient with triheptanoin to improve neurodevelopmental outcome. Design: Due to complex I deficiency and lack of response to the current standard therapy, we applied triheptanoin novel therapy. Methods: A 4-year-old male had compound heterozygous variants in ALDH7A1 and markedly elevated urine α-AASA. The goal dose of triheptanoin was 50% of the estimated energy requirement (EER). We assessed efficacy of triheptanoin using neuropsychological assessments. We measured 6-oxopipecolic acid using liquid chromatography tandem mass spectrometry. Results: Triheptanoin was started at 10 mL/day. There was nausea up to 3 weeks after each dose increase, which has improved allowing us to increase triheptanoin gradually. The maximum actual dose of triheptanoin was 40% of EER. Cognitive composite score improved from 16% to 63% on treatment. All chemistry and biochemical investigations were normal. 6-oxopipecolic acid levels did not normalize. Triheptanoin treatment seemed to be safe and tolerated well. Conclusion: Triheptanoin is an anaplerotic agent to provide substrates to the TCA cycle. This novel therapy improved neurodevelopmental outcome in our patient with PDE-ALDH7A1. We think that trihepatonoin should be the part of the current standard therapy to improve neurodevelopmental outcomes in patients with PDE-ALDH7A1.
Background: Primary Biliary Cholangitis (PBC) is a chronic, progressive liver disease. This paper outlines how a PBC patient registry was developed to address the gaps in evidence, care and policy affecting PBC patients in Ireland.Objectives: The PBC patient registry is designed to collect patient-reported data regarding medical history, pruritus, fatigue and quality of life of PBC patients living in Ireland. This data can be used to identify care and treatment gaps and ensure that the PBC patient voice is included in new treatment decisions and healthcare policy. This real-world data will support further scientific and clinical research, drive patient-led advocacy efforts and facilitate collaboration with the liver disease communities globally.Design: A patient-led, observational, registry-based study of PBC patients in Ireland.Methods and analysis: Participants must have a PBC diagnosis and be 18 years of age or older. PROMs (patient-reported outcome measures) were administered through a secure web-based system. After providing electronic informed consent, participants completed online data collection forms. These included demographic information, medical history, standard of care and validated PROMs for fatigue, pruritus and quality of life. This was followed by an anonymous survey to collect usability and comprehensiveness metadata.Ethics: The protocol was approved by TIER IRB Services, protocol ID: 5250715 (July 18th, 2025), which determined the study to be exempt as an observational, minimal-risk, non-interventional research activity involving anonymised patient-reported data.Discussion: At the time of publication, 52 participants were registered in the patient registry, of which 40 completed all data collection forms. The results of the post-completion survey suggest high satisfaction across the domains of usability, comprehension, relevance, privacy/confidentiality and overall experience. The PBC patient registry shows that web-based PROMs can be used to collect real-world evidence from patients. Participants reported that the system was easy to use and comprehensive, confirming the usability and effectiveness of this approach. It also provides a starting point to identify healthcare and treatment gaps and facilitates the inclusion of PBC patients' voices in national and international health policy decisions that affect them.Trial Registration: Not applicable.
Background:Late-onset Pompe disease (LOPD) is caused by a deficiency of the acid α-glucosidase enzyme. In LOPD treatment, enzyme replacement therapy is delivered via intravenous infusion, typically in clinical settings. Cipaglucosidase alfa is delivered with the oral enzyme stabilizer miglustat (cipa + mig). Objectives:Evaluate the safety of cipa + mig home infusions. Design:Post hoc analysis of pooled safety data from three clinical trials in adults with LOPD (NCT02675465, NCT03729362, NCT04138277). Methods:The frequency and severity of infusion-associated reactions (IARs) during cipa + mig home and clinic administration were analyzed. Results:In total, 65/151 patients (43.0%) received ⩾1 cipa + mig home treatment. Of 9185 treatments, 2024 (22.0%) were administered at home. IAR frequency was similar for home (1.3%, 26/2024) and clinic (1.8%, 129/7161). The most frequent IAR following home infusion was pyrexia (6.2% of patients). Two patients with ⩾1 home-based treatment experienced serious IARs. Conclusion:Analyses support the safety of home cipa + mig treatment in eligible adults with LOPD.
This review explores enzyme replacement therapies (ERTs) for lysosomal storage diseases (LSDs), focusing on disease characteristics, mechanisms of action, clinical benefits, limitations, and implications for patient care and access. LSDs are a group of over 50 rare, inherited metabolic disorders caused by mutations affecting lysosomal enzymes, membrane proteins, or transporters. This leads to the accumulation of undegraded macromolecules in tissues such as the CNS (central nervous system), heart, and muscles, resulting in progressive dysfunction and possible death. ERTs, approved by FDA (U.S. Food and Drug Administration) and the EMA (European Medicines Agency), have been the cornerstone of treatment since 1995, significantly improving the patient’s quality of life reducing organ damage and stabilizing cardiac and renal function. However, ERTs require lifelong intravenous infusions and have limited efficacy to treat CNS symptoms due to their inability to cross the BBB (blood–brain barrier). Some patients develop immune responses known as ADA (anti-drug antibody), which can compromise treatment effectiveness. Emerging research into nanotechnology and combination therapies may help overcome these limitations. Newer formulations such as pegunigalsidase (Elfabrio®) use for FD (Fabry disease), exhibit lower affinity for developing ADA compared to other ERTs, offer reduced immunogenicity and safety profiles enhancement. Cost remains a major barrier, with annual treatment expenses often exceeding hundreds of thousands of dollars. Access to ERT is uneven, particularly in underfunded healthcare systems. In North America, reimbursement varies by region and payer, potentially delaying treatment and impacting outcomes. This review draws from MEDLINE, Cochrane Reviews, and PubMed (1984–2025) using search terms such as LSDs, ERTs, rare diseases, Gaucher disease, Fabry disease, and others. Ongoing research and health policy reforms are essential to improve access, equity, and therapeutic outcomes for patients with LSDs.
Background:Rare diseases (RDs) encompass over 6000-8000 conditions, with 94% lacking available therapies. These conditions affect 400 million people globally, including three million Canadians, who face numerous challenges throughout their healthcare journey. Patient engagement (PE) is increasingly recognized as essential for improving outcomes yet remains inadequate in RD and orphan drug research particularly in Canada, where a national strategy for integrating RD patients' perspectives is lacking. To address this gap, this paper presents a Rare Disease Patient Engagement Framework (RDPEF), a structured model designed to support meaningful PE across all levels of healthcare, including research. Objectives:To develop a RDPEF that addresses barriers to engagement, reduces stigma, and incorporates patient experience as a core element in RD and orphan drug research and decision-making. Design:A conceptual framework development study informed by qualitative research and a targeted review of existing PE frameworks. Methods:The RDPEF was developed using a systematic approach that combined a review of existing literature on PE frameworks with new qualitative research on the experiences of RD patients in Canada. Semi-structured interviews examined patients' healthcare journeys, focusing on disease management, access to orphan drugs, and opportunities for engagement. A thematic analysis of the existing literature and interview data identified common challenges, which guided the framework's design. The RDPEF integrates elements from various other PE models, customizes them to the specific needs of RD patients, and emphasizes engagement across the entire orphan drug lifecycle. Results:Thematic findings from qualitative research highlighted limited to no patient involvement beyond clinical trials, significant stigma and discrimination, and the absence of structured engagement in drug review and reimbursement processes. These insights informed the development of the RDPEF, which outlines levels and forms of engagement, guiding principles (including stigma reduction), and mechanisms for integrating patient experience across healthcare, policy, and research domains. Conclusion:The RDPEF is a timely tool for enhancing PE in orphan drug research. By addressing engagement barriers, reducing stigma, and centering patient experience, the framework offers a roadmap for patients, researchers, healthcare providers, and policymakers to create a more inclusive and responsive system for RD patients in Canada.
Background:Kawasaki disease (KD) is a rare medium-sized vessel vasculitis that is the leading cause of acquired heart disease in children. However, most studies on KD focused on its occurrence in infants aged <6 months. Objectives:To evaluate the clinical characteristics, treatments, and complications of KD in Peruvian children. Design:Retrospective observational study. Methods:We collected data from patients aged <18 years who were diagnosed with KD and hospitalized at four healthcare institutions in Lima, Peru, between 2010 and 2022. Clinical characteristics, treatments, and complications were described overall and by age (groups A: <6 months, B: 6 to <12 months, C: 1 to <5 years, and D: ⩾5 years). Results:The median age was 2.3 years (interquartile range: 1.4-4, range: 1 month-13.2 years), and 68% were male. Group A had fewer oral mucocutaneous symptoms, whereas groups C and D had higher frequencies of cervical lymphadenopathy than the other groups. Gastrointestinal symptoms and incomplete KD presentation were common in groups A and D. Elevated white blood cell counts, platelet counts, erythrocyte sedimentation rates, and C-reactive protein levels were observed, particularly in patients with an illness duration of >10 days. A second dose of immunoglobulin was administered to 32 patients, and corticosteroids were administered to 48 patients (21.3%). Immunoglobulin resistance occurred in 14.8% of the patients, predominantly in group D. Coronary aneurysms were observed in 25 patients (12.1%), predominantly in group A. Two patients required intensive care unit admission, and no deaths occurred during hospitalization. Conclusion:Mucocutaneous manifestations of KD in Peruvian children are consistent with those reported in other populations. The frequency of aneurysms and immunoglobulin resistance differed according to age. We emphasize the importance of understanding the clinical presentation of KD, both overall and stratified by age, to prevent late diagnosis and ensure timely treatment.
What is this summary about? This summary describes the results of a research study (clinical trial) called ASPIRO that was published in the Lancet Neurology in 2023. This study looked at an investigational gene therapy called resamirigene bilparvovec (also known as AT132) as a possible treatment for children with a disease called X-linked myotubular myopathy (abbreviated as XLMTM).
Background:Fabry disease is a multisystemic lysosomal disorder caused by mutations in the GLA gene. Although traditionally attributed to lysosomal accumulation of globotriaosylceramide (Gb3), recent evidence suggests a key role of sustained systemic inflammation in its pathogenesis, even in early stages. Objectives:To characterize inflammatory and immunological profiles in a genetically stratified familial cohort with Fabry disease and explore genotype-dependent immune activation patterns. Design:Retrospective, longitudinal study of 11 patients from three interconnected families carrying distinct pathogenic GLA variants. Methods:We analyzed longitudinal data on inflammatory biomarkers (C-reactive protein, ferritin, fibrinogen) and immunological markers (IgG, IgM, IgE, complement C3/C4, anti-enzyme replacement therapy antibodies), alongside clinical variables. Multivariate correlation and unsupervised clustering techniques explored immunophenotypic patterns. Results:All patients exhibited chronic inflammation regardless of genotype. The c.53dup variant showed prominent humoral activation, IVS4+1G>A had complement-mediated activation with a cardiorenal phenotype, and c.845C>T showed mild persistent inflammation. Correlations included CRP and IgG, and complement factors with fibrinogen in the splicing variant group. Conclusion:Inflammation in Fabry disease is not merely a consequence of substrate accumulation but an active and early driver of disease. Preliminary inflammatory phenotypes based on immune mechanisms may guide future personalized therapeutic strategies.
What is this summary about? Sparsentan (FILSPARI®) is a once-daily pill for people with Immunoglobulin A (IgA) nephropathy who are at high risk for worsening kidney disease. Early results from a research study (clinical trial) called PROTECT showed that after 9 months of treatment, sparsentan lowered proteinuria more than irbesartan, a blood pressure medication commonly used to treat IgA nephropathy. These results contributed to sparsentan receiving approval in the United States, the European Union, Switzerland, and the United Kingdom in 2024. This is a plain language summary of publication of an original article published in The Lancet (a medical journal) in November 2023, which reported further results from the PROTECT study. The original article reported on how well sparsentan worked to lower proteinuria and slow the worsening of kidney function (measured by estimated glomerular filtration rate (eGFR)) in people with IgA nephropathy compared with the highest possible dose of irbesartan over an approximately 2-year treatment period. The article also described the side effects that people enrolled in this study had with either sparsentan or irbesartan.
